The development of novel catalytic systems exhibiting unique reactivity and high enantioselectivity requires the synthesis of chiral ligands for transition metals. Generally, some of the most successful chiral ligands have been chelating phosphines possessing a C.sub.2 symmetry axis. The synthesis of these phosphines in optically pure form often involves tedious synthetic routes that are limited to only one antipode or require a resolution step.
One synthetic route is through a diol intermediate. S. Masamune et al., Journal of Organic Chemistry, Vol. 54, p. 1755 (1989) teaches use of Baker's yeast for the reduction of 2,5-hexanedione to the corresponding (S,S)-diol, followed by reaction with methanesulfonyl chloride and ring closure with benzylamine to form the optically pure (2R,5R)-2,5-dimethylpyrrolidine. Wilson et al., Synlett, pp. 199-200, April (1990) disclose similar use of a diol intermediate formed via a Baker's yeast reduction of a diketone in the preparation of a 2,5-dimethylphospholane (Compound 10). The phospholane is prepared by reacting the diol with methanesulfonyl chloride followed by phenylphosphine in the presence of potassium hydroxide. However, enzymatic reductions generally provide only one enantiomer of the desired product, and can have limitations such as high substrate specificity, low product yields, or involved isolation procedures.
In addition, many of the chiral phosphines known in the art have at least two aryl substituents on the phosphorus, rendering that center relatively electron poor. The mechanism of asymmetric induction using these phosphines has been linked to the proper conformational relationship between the phenyl groups on the phosphorus centers.
More recently, chiral phosphines having relatively electron-rich phosphorus centers have been reported. Brunner et al., Journal of Organometallic Chemistry, Vol. 328, PP 71-80 (1987) teach 3,4-disubstituted phospholanes derived from tartaric acid having chloro, methoxy, or dimethylamino substituents. These were complexed with manganese and rhodium and used as catalysts in the hydrogenation of alpha-N-acetamidocinnamic acid. Relatively low optical yields of (S)-N-acetylphenylalanine of from 6.6% enantiomeric excess to 16.8% enantiomeric excess were obtained.
A need exists for transition metal complexes providing high levels of stereochemical control and asymmetric induction in stoichiometric and catalytic transformations. A need also exists for efficient synthetic routes for the preparation of chiral ligands having a high degree of enantiomeric purity for transition metal catalysts.
It is therefore an object of the present invention to provide novel phospholane compounds as chiral ligands for transition metals.
It is a further object of the present invention to provide transition metal catalysts which provide high levels of stereochemical control of reactions.
It is a further object of the present invention to provide transition metal catalysts which result in high levels of asymmetric induction in hydrogenation reactions.
It is a further object of the present invention to provide efficient synthetic routes for the preparation of these phospholane compounds.